Statin drugs are currently the most therapeutically effective drugs available for reducing the level of LDL in the blood stream of a patient at risk for cardiovascular disease. This class of drugs includes pravastatin as well as compactin, lovastatin, simvastatin, fluvastatin and atorvastatin.
Pravastatin is the common medicinal name of the chemical compound [1S-[1α(β*,δ*)2α,6α,8β(R*),8aα]]-1,2,6,7,8,8a-hexahydro-β, δ, 6-trihydroxy-2-methyl-8-(2-methyl-1-oxobutoxy)-1-naphthalene-heptanoic acid. (CAS Registry No. 81093-370.) The molecular structure of pravastatin is represented by Formula (Ia) where R═OH. The lactone form is represented by Formula (Ib), with atoms labeled to indicate numbering of the atoms. 
Pravastatin, compactin (Formula Ia, R═H), lovastatin (Formula Ia, R═CH3), simvastatin, fluvastatin and atorvastatin each possess an alkyl chain that is terminated by a carboxylic acid group and that bears two hydroxyl groups at the β and δ positions with respect to the carboxylic acid group. The carboxylic acid group and the hydroxyl group at the δ position are prone to lactonize as shown in formula (Ib). Lactonizable compounds like the statins may exist in the free acid form or the lactone form or as an equilibrium mixture of both forms. Lactonization causes processing difficulties in the manufacture of statin drugs because the free acid and the lactone forms of the compounds have different polarities. A method of purifying one form is likely to remove the other form along with the impurities resulting in a lower yield. Consequently, great care must ordinarily be exercised when handling lactonizable compounds in order to isolate them in high yield.
Presently, the most economically feasible method of making pravastatin is by microbial hydroxylation of compactin at the C-6 position. Although enzymatic processes are highly stereoselective, it is common for pravastatin sodium obtained after isolation from a fermenation broth to be contaminated with a significant amount of the C-6 epimer of pravastatin (“epiprava”). The C-6 position is bis-allylic and, hence, the C-6 atom is prone to epimerize. Careful control of pH and other conditions during isolation of pravastatin is required in order to minimize epimerization. Known methods of isolating pravastatin from a fermentation broth either are ill-suited for isolating pravastatin as its sodium salt or produce pravastatin sodium contaminated with significant amounts of pravastatin lactone and/or epiprava. The present invention meets a need in the art for an efficient method of isolating pravastatin sodium from a fermentation broth in high purity, in high yield, on a preparative scale and without the need for chromatographic purification.